Hailing from Stoney Creek, Ontario, Popowich landed his first professional acting role at the age of 15 when he was cast in the 1988 independent Canadian film Tommy Tricker and the Stamp Traveller. Four years later, he and future Deep Space Nine star Nicole de Boer worked together as regulars on the Canadian television series Catwalk. This series, which focused on a struggling band of young musicians, ran from October 1992 through January 1994. Popowich and de Boer would work together again ten years later in the 2004 science fiction comedy, Phil the Alien.

Popowich made the transition to American television when he received a supporting role in the 1997 Lifetime made-for-TV movie Any Mother's Son. Shortly thereafter, he was given a recurring role as Jasper McQuade on the popular series Beverly Hills, 90210. This was followed with his appearance on Deep Space Nine followed by guest spots on Unhappily Ever After (starring Nikki Cox, including an episode with fellow DS9 guest star Faith C. Salie), Nash Bridges, and the CBS series Promised Land. He also appeared in the 1999 TV movie Pirates of Silicon Valley with fellow Star Trek alumni J.G. Hertzler, Nikita Ager, Alexander Enberg, Jeffrey Nordling, Kitty Swink, and Marc Worden.

Popowich starred in the 2000 independent film Silver Man, playing the title role and co-starring with DS9's Louise Fletcher. Also in 2000, Popowich appeared in the pilot episode for James Cameron'sDark Angel, along with Stanley Kamel and John Savage. During the 2000-2001 TV season, Popowich starred as an angel known as "Mr. Smith" in the second season of the PAX series Twice in a Lifetime. Popowich worked with Star Trek: The Next Generation star Wil Wheaton in the last episode of this series. Popowich's subsequent credits include a supporting role in the 2003 film Vlad (with Brad Dourif, Guy Siner, and John Rhys-Davies), appearances on Showtime's The L Word, and a recurring role on the NBC series Angela's Eyes, as well as recurring roles on Degrassi: The Next Generation and the CBC drama Cracked.

He also starred in the police drama The Bridge as Tommy Dunn with Battlestar Galactica's Aaron Douglas. Popowich also played JR Godfrey in season 1 of the Netflix horror series Hemlock Grove, where he again worked with Aaron Douglas.